Environmental stress can induce an increase in the rate of synthesis of so-called heat shock, or stress, proteins in both procaryotic and eucaryotic cells [see for example Schlesinger et al (eds) in Heat Shock from Bacteria to Man, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y. (1972)]. Although the function of stress proteins has yet to be finally resolved, some have been reported to participate in assembly and structural stabilisation of cerain cellular and viral proteins, and their presence at high concentration may have an additional stabilising effect during exposure to adverse conditions.
Many pathogenic organisms have been shown to produce stress proteins [see for example Young D, et al, Proc. Natl. Acad. Sci. USA 85, 4267-4270 (1988)]. The proteins are thought to be produced in response to the stress of infection to help protect the invading pathogen. Thus, for example, the ability to produce stress proteins has been implicated in the survival of bacterial pathogens within macrophages [Christmas, M. F. et al, Cell, 41, 753-762 (1985) and Morgan, R. W. et al, Proc. Natl. Acad. Sci. USA, 83, 8059-8063, (1986)].
It has been suggested that the presence of stress proteins in a variety of human pathogens indicates that the stress response is a general component of infections, and that stress proteins should be considered among candidates for subunit vaccines [Yound, D. et al, ibid].
Candida albicans is, medically, the most important of the human fungal pathogens. Systemic candidiasis (candidosis) is an increasingly common cause of death amongst immunocompromised and debilitated patients, with a mortality of over 70% [Gold, J. W. M., Am. J. Med. 76, 458-463, (1984)]; while oral candidiasis is a frequent early manifestation of the acquired immunodeficiency syndrome [Klein, R. S. et al, N. Engl. J. Med. 311, 354-357, (1984)]. Candidiasis is difficult to diagnose, and is not easy to treat, mainly since the usual method of treatment involves use of amphotericin B, which is itself highly toxic. A need therefore exists in the diagnosis and treatment of Candida infections for more sensitive diagnostic methods and treatment which has less toxic side effects.
A number of Candida antigens have been detected in the sera of patients with systemic candidiasis [Matthews, R. C. et al, J. Clin. Microbiol. 25, 230-237 (1987)]. One of these, with a relative molecular mass of approximately 47 kilodaltons (47 kd) is an immunodominant antigen which has been reported by four independent groups [Matthews R. C., et al Lancet ii, 1415-1418 (1984); Au-Yound, J K et al, Diagn. Microbiol. Infect. Dis., 3, 419-432, (1985); Neale T. J., et al. Aust. N.Z.J. Med., 17, 201-209 (1987); and Ferreira R. P. et al, J. Clin. Microbiol. 28, 1075-1078 (1990)]. This 47 kd antigen is distinct from the 48-52 Kd antigen described by Strockbine et al [Strockbine N. A. et al Infect. Immun. 43, 715-721 (1984)] for two reasons:
(1) monoclonal antibodies raised against the 48-52 Kd antigen cross-react with antigens at 120-135 Kd and 35-38 Kd [Strockbine N. A. et al, Infect Immun 43, 1012-18 (1984); Buckley H. R., et al U.S. Pat. No. 4,670,382 (1987)] and PA1 (2) the 48-52 Kd antigen it is an enolase [Safranek W. W. and Buckley H. R., Second Conference on Candida and Candidiasis, Abstract A7 (1990)]. In contrast, antibody to the 47 Kd antigen cross-reacts with an antigen at about 92 Kd (see below). An immundominant C. albicans antigen of 54.3 Kd (range 48.9 to 59.7 Kd) was described by Greenfield R. A., and Jones J. M., in Infect. Immun. 34, 469-477 (1981). PA1 (1) it has an isoelectric point (pI) in a range around pI 4 to pI 5; PA1 (2) it is an immunodominant conserved antigen; PA1 (3) patients recovering from systemic candidiasis seroconvert to the stress protein; PA1 (4) patients with acquired immunodeficiency syndrome have antibody to the stress protein; PA1 (5) it cross-reacts with the 47 kilodalton and approximately 92 kilodalton antigens of Candida albicans using affinity-purified polyclonal monospecific antibody against the 47 kilodalton antigen.